Expression of glucose transporters in human neurodegenerative diseases

Głuchowska, Kinga; Pliszka, Monika; Szablewski, Leszek

doi:10.1016/j.bbrc.2020.12.067

Cited by 24 publications

(18 citation statements)

References 126 publications

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“…Among commonly used SGLT2i, Cana has the least specificity and can potentially inhibit both SGLT1 and SGLT2 transporters (Ohgaki et al 2016). SGLT1 and SGLT2 have been detected in many areas of the brain (Głuchowska et al 2021). Brain expression of SGLT2 is lower than SGLT1 but was detected in the microvessels of the blood-brain barrier (BBB), hippocampus pyramidal and granular cells, and astrocytes in the ventromedial hypothalamus (Poppe et al 1997;Fan et al 2015;Tahara et al 2016;Nguyen et al 2020).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of Canagliflozin: lessons from aged genetically diverse UM-HET3 mice

Jayarathne

Debarba

Jaboro

et al. 2022

Preprint

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The aging brain is characterized by a progressive increase in neuroinflammation and central insulin resistance, which contribute to neurodegenerative diseases and cognitive impairment. Recently, the Interventions Testing Program (ITP) demonstrated that the anti-diabetes drug, Canagliflozin (Cana), a sodium-glucose transporter 2 inhibitor (SGLT2i), led to lower fasting glucose and improved glucose tolerance in both sexes, but extended median lifespan by 14% only in male mice. Here we show that Cana treatment significantly improved central insulin sensitivity in the hypothalamus and the hippocampus of 30-month-old male mice. Remarkably, Cana-treated mice showed significant reductions in age-associated hypothalamic gliosis with a decrease in inflammatory cytokine production by microglia in both sexes. In the hippocampus, Cana reduced microgliosis and astrogliosis in males, but not in female mice. The decrease in microgliosis was partially dependent on mTOR signaling, as evidenced by reduced phosphorylation of S6 kinase in microglia of Cana-treated aged male, but not female mice. Remarkably, Cana treatment improved exploratory and locomotor activity of 30-month-old male but not female mice. Taken together, our findings demonstrate sex-specific neuroprotective effects of Cana treatment, suggesting its application for the potential treatment of neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of Canagliflozin: lessons from aged genetically diverse UM-HET3 mice

Jayarathne

Debarba

Jaboro

et al. 2022

Preprint

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“…For example, hypometabolism of glucose due to a decrease in expression of glucose transporters in the brain occurs in Alzheimer's disease [97]. Similarly, energy and glucose metabolism disturbances are suggested to play a role in the development of Huntington's disease pathology [98]. The human brain expresses ten different sodium-independent glucose transporters (GLUTs), which in conjunction with sodium-dependent glucose cotransporters (SGLTs) and uniporter SWEET protein, are responsible for glucose uptake.…”

Section: Punicic Acid Induced a Higher Expression Of Glut4mentioning

confidence: 99%

“…GLUT4 is an insulin-sensitive glucose transporter expressed in the hypothalamus, sensorimotor cortex, hippocampus, and pituitary. Its physiological role is unknown, but some of its suggested functions are its involvement in glucose sensing, the insulin modulation of glucose transport in distinct brain areas, and the transport of glucose, in case of high demand, to the motor neurons [97,98].…”

Section: Punicic Acid Induced a Higher Expression Of Glut4mentioning

confidence: 99%

“…In Alzheimer's, along with decreased glucose uptake in highly active areas of the brain such as the cortex, hippocampus, and cerebral microvessels, glucose transporters (GLUT) decrease [98,99]. Impaired expression of GLUT-4 in the hippocampal neurons could be related to short-term memory loss and disorientation in Alzheimer patients [100].…”

Section: Punicic Acid Induced a Higher Expression Of Glut4mentioning

confidence: 99%

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Punicic Acid and Its Role in the Prevention of Neurological Disorders: A Review

Guerra-Vázquez

Martínez-Ávila

Guajardo‐Flores

et al. 2022

Foods

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Millions of people worldwide are affected by neurodegenerative diseases (NDs). NDs are characterized by progressive damage and death of nerve cells accompanied by high levels of inflammatory biomarkers and oxidative stress conditions. Punicic acid, the main bioactive component of pomegranate (Punica granatum) seed oil, is an omega-5 isomer of conjugated α-linoleic acid that has shown strong anti-oxidative and anti-inflammatory effects that contributes towards its positive effect against a wide arrange of diseases. Punicic acid decreases oxidative damage and inflammation by increasing the expression of peroxisome proliferator-activated receptors. In addition, it can reduce beta-amyloid deposits formation and tau hyperphosphorylation by increasing the expression of GLUT4 protein and the inhibition of calpain hyperactivation. Microencapsulated pomegranate, with high levels of punicic acid, increases antioxidant PON1 activity in HDL. Likewise, encapsulated pomegranate formulations with high levels of punicic acid have shown an increase in the antioxidant PON1 activity in HDL. Because of the limited brain permeability of punicic acid, diverse delivery formulations have been developed to enhance the biological activity of punicic acid in the brain, diminishing neurological disorders symptoms. Punicic acid is an important nutraceutical compound in the prevention and treatment of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease.

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“…Importantly, glucose transporter expression significantly changes in response to energy demands or under pathophysiological conditions; indeed, brain GLUT1 and GLUT3 protein levels are considerably lower in AD patients and animal models of AD (20) . In STZ-induced diabetic rats, GLUT3 protein expression was specifically upregulated in the hippocampus, whereas GLUT1 protein abundance was similar to that of nondiabetic littermates (21,22).…”

Section: Introductionmentioning

confidence: 99%

Recurrent moderate hypoglycemia accelerates the progression of Alzheimer’s disease through impairment of the TRPC6/GLUT3 pathway

He¹,

Li²,

Cui³

et al. 2022

JCI Insight

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Currently, the most effective strategy for dealing with Alzheimer's disease (AD) is delaying the onset of dementia. Severe hypoglycemia is strongly associated with dementia; however, the effects of recurrent moderate hypoglycemia (RH) on progression of cognitive deficits in diabetic patients with genetic susceptibility to AD remain unclear. Here, we report that insulin-controlled hyperglycemia only slightly aggravated AD-type pathologies and cognitive impairment; however, RH significantly increased neuronal hyperactivity and accelerated the progression of cognitive deficits in streptozotocin(STZ)-induced diabetic APP/PS1 mice. GLUT3-mediated neuronal glucose uptake was not significantly altered under hyperglycemia, but was markedly reduced by RH, which induced excessive mitochondrial fission in the hippocampus.Overexpression of GLUT3 specifically in DG area of hippocampus enhanced mitochondrial function and improved cognitive deficits induced by RH. Activation of TRPC6 increased GLUT3-mediated glucose uptake in brain and alleviated RH-induced cognitive deficits, and inactivation of Ca 2+ /AMPK pathway was responsible for TRPC6-induced GLUT3 inhibition. Taken together, RH impairs brain GLUT3-mediated glucose uptake and further provokes neuronal mitochondrial dysfunction by inhibiting TRPC6 expression, which then accelerates progression of cognitive deficits in diabetic APP/PS1 mice. Avoiding RH is essential for glycemic control in diabetic patients, and TRPC6/GLUT3 represent potent targets for delaying the onset of dementia in diabetic patients.

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Expression of glucose transporters in human neurodegenerative diseases

Cited by 24 publications

References 126 publications

Neuroprotective effects of Canagliflozin: lessons from aged genetically diverse UM-HET3 mice

Neuroprotective effects of Canagliflozin: lessons from aged genetically diverse UM-HET3 mice

Punicic Acid and Its Role in the Prevention of Neurological Disorders: A Review

Recurrent moderate hypoglycemia accelerates the progression of Alzheimer’s disease through impairment of the TRPC6/GLUT3 pathway

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